Impairment of CD4+ T Cell Polarization by Dengue Virus–Infected Dendritic Cells
AJ Chase, FA Medina… - Journal of Infectious …, 2011 - academic.oup.com
AJ Chase, FA Medina, JL Muñoz-Jordán
Journal of Infectious Diseases, 2011•academic.oup.comBackground. The production of type I interferon alpha/beta (IFN-α/β) is crucial to viral
clearance during dengue virus (DENV) infection; however, in vitro–infected dendritic cells
(DCs) exhibit a decreased capacity to respond to IFN-α/β stimulation, and antigen-
presenting cells (APCs) isolated from patients with acute DENV infection exhibit defects in T
cell priming. Methods. In order to ascertain the stimulatory capacity of primary human
monocyte-derived DCs infected with wild-type DENV isolates, representing a range of …
clearance during dengue virus (DENV) infection; however, in vitro–infected dendritic cells
(DCs) exhibit a decreased capacity to respond to IFN-α/β stimulation, and antigen-
presenting cells (APCs) isolated from patients with acute DENV infection exhibit defects in T
cell priming. Methods. In order to ascertain the stimulatory capacity of primary human
monocyte-derived DCs infected with wild-type DENV isolates, representing a range of …
Abstract
Background. The production of type I interferon alpha/beta (IFN-α/β) is crucial to viral clearance during dengue virus (DENV) infection; however, in vitro–infected dendritic cells (DCs) exhibit a decreased capacity to respond to IFN-α/β stimulation, and antigen-presenting cells (APCs) isolated from patients with acute DENV infection exhibit defects in T cell priming.
Methods. In order to ascertain the stimulatory capacity of primary human monocyte-derived DCs infected with wild-type DENV isolates, representing a range of genotypes and disease outcomes, we cocultured infected DCs with allogeneic-naive CD4+ T cells. The gene expression patterns of IFN-α/β sensitive genes were quantitated to determine if the infected DCs displayed a blunted IFN-α/β response.
Results. DENV-infected DCs induced the initial proliferation of naive CD4+ T cells but they remained nonpolarized in effector function. The expression of IFN-α/β–stimulated genes was downregulated, revealing that the inhibition of IFN-α/β signaling is conserved among endemic DENV serotype 2 strains.
Conclusions. The failure of naive CD4+ T cells to differentiate into IFN gamma-producing effector T cells when primed by DENV-infected DCs cannot be explained solely by a block in IFN-α/β signaling, suggesting that the ability of DENV to evade the early host response is multifaceted.
Oxford University Press